Theoretical studies of low-energy positron-atom and atom-antiatom collisions

Theoretical studies of low-energy positron collisions with various one-electron models of the helium atom have been made using the Kohn variational method in order to find out if such a model atom is capable of yielding accurate cross sections for elastic scattering, positronium (Ps) formation and annihilation. For positron-helium scattering, comparisons are made with the accurate results obtained from the ab initio variational calculations of Van Reeth and Humberston. All the models provide qualitatively accurate results over some energy intervals. Although one model gives excellent values for the elastic scattering cross section up to the Ps formation threshold, it is affected by a resonance near the threshold. None of the models yields very accurate results for the annihilation cross section, although a comparatively crude model reproduces the accurate distribution function for the Doppler broadening of the annihilation γ-ray energy spectrum. A correlation has been found by Van Reeth et al between the Ps formation cross section and the associated threshold energy for the noble gas atoms. A parameter in the correlation equation has been interpreted as the Ps formation cross section for an atom with a zero threshold energy, so Ps formation cross sections have been calculated for such a model atom. The results obtained compare reasonably favourably with the energy dependence of this parameter obtained from experimental data. An adiabatic model has also been used to study hydrogen-antihydrogen collisions, and further studies may involve a model one-electron atom in the study of helium-antihydrogen collisions. The results are satisfactory, but further investigations are needed to include the rearrangement of the atom-antiatom system into positronium and protonium

Effects of two contrasting canopy manipulations on growth and water use of London plane (Platanus x acerifolia) trees

Aims: Two contrasting canopy manipulations were compared to unpruned controls on London plane trees, to determine the effects on canopy regrowth, soil and leaf water relations. Methods: ‘Canopy reduction’, was achieved by removing the outer 30 % length of all major branches and ‘canopy thinning’, by removing 30 % of lateral branches arising from major branches. Results: Total canopy leaf areas recovered within two and three years of pruning for the canopy-thinned and reduced trees respectively. Canopy reduction increased mean leaf size, nitrogen concentration, canopy leaf area density and conserved soil moisture for up to 3 years, whereas canopy thinning had no effects. Another experiment compared more severe canopy reduction to unpruned trees. This produced a similar growth response to the previous experiment, but soil moisture was conserved nearer to the trunk. Analysis of 13C and 18O signals along with leaf water relations and soil moisture data suggested that lower boundary layer conductance within the canopy-reduced trees restricted tree water use, whereas for the canopy-thinned trees the opposite occurred. Conclusions: Only canopy reduction conserved soil moisture and this was due to a combination of reduced total canopy leaf area and structural changes in canopy architecture

Probing the functional tolerance of the b subunit of Escherichia coli ATP synthase for sequence manipulation through a chimera approach.

A dimer of 156-residue b subunits forms the peripheral stator stalk of eubacterial ATP synthase. Dimerization is mediated by a sequence with an unusual 11-residue (hendecad) repeat pattern, implying a right-handed coiled coil structure. We investigated the potential for producing functional chimeras in the b subunit of Escherichia coli ATP synthase by replacing parts of its sequence with corresponding regions of the b subunits from other eubacteria, sequences from other polypeptides having similar hendecad patterns, and sequences forming left-handed coiled coils. Replacement of positions 55-110 with corresponding sequences from Bacillus subtilis and Thermotoga maritima b subunits resulted in fully functional chimeras, judged by support of growth on nonfermentable carbon sources. Extension of the T. maritima sequence N-terminally to position 37 or C-terminally to position 124 resulted in slower but significant growth, indicating retention of some capacity for oxidative phosphorylation. Portions of the dimerization domain between 55 and 95 could be functionally replaced by segments from two other proteins having a hendecad pattern, the distantly related E subunit of the Chlamydia pneumoniae V-type ATPase and the unrelated Ag84 protein of Mycobacterium tuberculosis. Extension of such sequences to position 110 resulted in loss of function. None of the chimeras that incorporated the leucine zipper of yeast GCN4, or other left-handed coiled coils, supported oxidative phosphorylation, but substantial ATP-dependent proton pumping was observed in membrane vesicles prepared from cells expressing such chimeras. Characterization of chimeric soluble b polypeptides in vitro showed their retention of a predominantly helical structure. The T. maritima b subunit chimera melted cooperatively with a midpoint more than 20 degrees C higher than the normal E. coli sequence. The GCN4 construct melted at a similarly high temperature, but with much reduced cooperativity, suggesting a degree of structural disruption. These studies provide insight into the structural and sequential requirements for stator stalk function

Pharmacologically blocking p53-dependent apoptosis protects intestinal stem cells and mice from radiation.

Exposure to high levels of ionizing radiation (IR) leads to debilitating and dose-limiting gastrointestinal (GI) toxicity. Using three-dimensional mouse crypt culture, we demonstrated that p53 target PUMA mediates radiation-induced apoptosis via a cell-intrinsic mechanism, and identified the GSK-3 inhibitor CHIR99021 as a potent radioprotector. CHIR99021 treatment improved Lgr5+ cell survival and crypt regeneration after radiation in culture and mice. CHIR99021 treatment specifically blocked apoptosis and PUMA induction and K120 acetylation of p53 mediated by acetyl-transferase Tip60, while it had no effect on p53 stabilization, phosphorylation or p21 induction. CHIR99021 also protected human intestinal cultures from radiation by PUMA but not p21 suppression. These results demonstrate that p53 posttranslational modifications play a key role in the pathological and apoptotic response of the intestinal stem cells to radiation and can be targeted pharmacologically

Developing Hyperpolarized 13C Spectroscopy and Imaging for Metabolic Studies in the Isolated Perfused Rat Heart

Hyperpolarized 13C magnetic resonance is a powerful tool for the study of cardiac metabolism. In this work, we have implemented protocols for the real-time hyperpolarized 13C investigation of Langendorff-perfused rat hearts using both non-selective non-localized spectroscopy and fast spectroscopic imaging. Following [1-13C] pyruvate infusion, we observed both catabolic and anaplerotic metabolic processes resulting in a number of metabolites, including bicarbonate, carbon dioxide, lactate, alanine and aspartate. Employing fast spectroscopic imaging, we were able to observe regional variations in pyruvate perfusion as well as in lactate and bicarbonate productio

Ocular tolerability and efficacy of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis: primary 6-month results of the SAVE Study.

BACKGROUND: The purpose of this study is to evaluate the ocular tolerability and efficacy of sirolimus administered as subconjunctival or intravitreal injections in patients with non-infectious uveitis. Sirolimus as a Therapeutic Approach for Uveitis (SAVE) is a prospective, randomized, open-label, interventional study. Thirty patients were enrolled and randomized in 1:1 ratio to receive either intravitreal injections of 352 μg sirolimus or subconjunctival injections of 1,320 μg at days 0, 60, and 120, with primary endpoint at month 6. RESULTS: At month 6, all subjects with active uveitis at baseline showed reduction in vitreous haze of one or more steps. Forty percent of subjects showed reduction of two steps or more of vitreous haze (four in each group), and 60% showed a reduction of one-step vitreous haze (seven in group 1 and five in group 2). Changes in the inflammatory indices were statistically significant (p \u3c 0.05) in both study groups. Thirty percent of patients gained one or more lines of visual acuity, 20% lost one or more lines, and 50% maintained the same visual acuity. There were no statistically significant differences between the two study groups at month 6. No serious adverse events were found to be related to the study drug. CONCLUSION: Local administration of sirolimus, either intravitreally or subconjunctivally, appears to be safe and tolerable. No drug-related systemic adverse events or serious adverse events were noted. Sirolimus delivered as either an intravitreal or subconjunctival injection has demonstrated bioactivity as an immunomodulatory and corticosteroid-sparing agent in reducing vitreous haze and cells, improving visual acuity, and in decreasing the need for systemic corticosteroids

MetaCyto: A Tool for Automated Meta-analysis of Mass and Flow Cytometry Data

While meta-analysis has demonstrated increased statistical power and more robust estimations in studies, the application of this commonly accepted methodology to cytometry data has been challenging. Different cytometry studies often involve diverse sets of markers. Moreover, the detected values of the same marker are inconsistent between studies due to different experimental designs and cytometer configurations. As a result, the cell subsets identified by existing auto-gating methods cannot be directly compared across studies. We developed MetaCyto for automated meta-analysis of both flow and mass cytometry (CyTOF) data. By combining clustering methods with a silhouette scanning method, MetaCyto is able to identify commonly labeled cell subsets across studies, thus enabling meta-analysis. Applying MetaCyto across a set of ten heterogeneous cytometry studies totaling 2,926 samples enabled us to identify multiple cell populations exhibiting differences in abundance between demographic groups

Developing hyperpolarized 13C spectroscopy and imaging for metabolic studies in the isolated perfused rat heart

Hyperpolarized 13C magnetic resonance is a powerful tool for the study of cardiac metabolism. In this work, we have implemented protocols for the real-time hyperpolarized 13C investigation of Langendorff-perfused rat hearts using both non-selective non-localized spectroscopy and fast spectroscopic imaging. Following [1-13C] pyruvate infusion, we observed both catabolic and anaplerotic metabolic processes resulting in a number of metabolites, including bicarbonate, carbon dioxide, lactate, alanine and aspartate. Employing fast spectroscopic imaging, we were able to observe regional variations in pyruvate perfusion as well as in lactate and bicarbonate production